Method for obtaining pioglitazone as an antidiabetic agent

A method for obtaining the antidiabetic of formula I

• comprising
• condensing a compound of formula III where Z is a leaving group with a compound of formula II where R1 is a protecting group
• to form an ether of formula IV:
• removing protecting group R1 from formula IV to form an aniline of formula V:
• converting the aniline of formula V to a diazonium salt,
• reacting the diazonium salt with an olefin of formula VI where R2 is an electron withdrawing group
• to form an alkyl halide of formula VII:
• reacting the alkyl halide of formula VII with thiourea to form an imine of formula VIII:
• and,
• hydrolyzing the imine of formula VIII to give the antidiabetic of formula I;
• wherein
• the leaving group Z is a radical of the formula
• wherein A, which may be substituted or unsubstituted, is an aryl or an alkyl group;
• wherein M is hydrogen or an alkali metal;
• wherein the protecting group R1 is selected from the group consisting of an acyl group derived from lower aliphatic acids (C1–C4), an acyl group derived from lower aromatic acids, n-alkyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, alloxycarbonyl, 2-cyanoethoxycarbonyl, dimethylaminomethylenyl, and hexa-2,4-dien-2,5-diyl;
• wherein m is 0 or 1;
• wherein when m=1, R=Br;
• wherein the electron withdrawing group R2 is selected from the group consisting of a cyano group, a carboxylic acid, an ester, and the salt of a carboxylic acid;
• and wherein X is a halogen atom.